Introduction to Analgesic Drugs - NSAIDs

Question 1

What are the 3 therapeutic effects of NSAIDs?

Answer 1

• Anti-inflammatory
• Analgesic
• Antipyretic

Question 2

What is the molecular mechanism of action?

Answer 2

To inhibit the COX (cyclooxygenase) enzyme (primary but not sole action); thus preventing PG and thromboxane (prostanoids) synthesis from arachidonic acid.

Question 3

What is the difference in roles between the COX-1 and COX-2 enzymes?

Answer 3

COX-1; constitutive and products involved in signalling and homeostasis; ‘housekeeping’ role.
COX-2; induced part of the inflammatory response.

Question 4

What are the actions of prostanoids (e.g. PGE2)?

Answer 4

• PGE2 is produced in abundance in inflammation; recruits receptors such as EP receptors
• EP receptors cause sensitisation of primary afferents (nociceptors); indirect mechanism making one more aware of pain (potential allodynia-esque).

Question 5

What do PGs enhance the function of?

Answer 5

• Bradykinin receptors
• TRPV1 channels
• P2X receptors
  etc.

Question 6

What issues (cautions/contraindications) are associated with NSAIDs?

Answer 6

• Gastric ulceration (give PPI)
• Aspin-induced asthma
• Kidney impairment
• Ischaemic heart disease
• Cardiac failure
• Coagulation defects
• Peripheral arterial disease

Question 7

What are the most common unwanted/side effects of NSAIDs?

Answer 7

• GIT disturbances: dyspepsia, diarrhoea, gastric bleeding (reduction of prostanoids that promote clotting and gastric mucosa protection in COX-1)
• Skin reactions 2nd most common
• Renal damage (particularly in elderly/kidney disease patients)
• ‘Analgesic neuropathy’ in chronic heavy users (nephritis; inflammation of kidneys, renal necrosis)
• Bronchospasm in ‘aspirin sensitive’ asthmatic

Question 8

How do the sites of action of NSAIDs and opioids differ?

Answer 8

NSAIDs: just before mediator release interrupting the sensitisation process
Opioids: in the descending inhibitory pathways in the spine influencing the central terminal/dorsal root, the excitation of the neurone (K+/Ca2+ etc.) and potentially interrupting neuropeptide release.

Question 9

What are the 3 steps of the NICE/WHO pain ladder?

NRS = Numeric Rating Scale

Answer 9

1. Mild pain 6/10 NRS)

- Strong opioids: morphine, diamorphine, fentanyl, hydromorphone, oxycodone.